Oseltamivir Phosphate

Colorized transmission electron micrograph of an influenza virus particle. Anti-influenza medications, such as oseltamivir phosphate, can be used to treat or prevent the flu. Source: CDC/Dr. Erskine; L. Palmer; Dr. M. L. Martin.

Other Names

• Tamiflu (US)

Uses

Treatment of influenza

Oseltamivir phosphate is used to treat uncomplicated illness due to influenza infection in adults and children at least one year old, who have had symptoms of the flu for no more than two days. In people who have had flu symptoms for more than two days, oseltamivir phosphate and other drugs in its class are not effective in improving symptoms or shortening the length of illness.

Prevention of influenza

Oseltamivir phosphate is also used to prevent someone from catching the flu if they have been exposed to another person with influenza, or in cases where there has been an outbreak of the flu in the community.

How Oseltamivir Phosphate Is Taken

Oseltamivir phosphate is available as capsules containing 30 mg, 45 mg, or 70 mg and as an oral solution containing 12 mg/mL of the active drug. Capsules and the oral solution are taken by mouth with or without food. The drug may be better tolerated when taken with food. The oral solution can be used in young children and in older people who cannot swallow capsules. If the oral solution is not available, capsules may be opened and the contents mixed with a sweetened liquid.^[1]

Specific dose guidelines are as follows:

• For adults and adolescents 13 years of age and older.

• Treatment of influenza: the recommended dose is 75 mg taken twice a day for five days. Treatment should begin within two days of the start of flu symptoms.
• Prevention of influenza: the recommended dose is 75 mg taken once a day for at least 10 days. The drug should be started within two days of exposure to the flu virus.

• For children between the ages of 1 and 13 years of age.

The recommended dose is based on weight as shown in the following table and should be started within two days of the start of symptoms (Treatment) or exposure to the virus (Prevention).

If your doctor prescribes Tamiflu® capsules for your child and your child cannot swallow them, this video describes how to mix the contents of the capsules with a sweet thick liquid so they can be given that way.

How It Works

Oseltamivir phosphate is in a class of drugs called neuraminidase inhibitors.^{[2] [3]} They work by preventing the influenza A and influenza B viruses from budding off of human cells. In order for the flu virus to cause disease, it must make copies of itself inside human cells. These copies are then released from the cell by budding and can go on to infect other human cells. The neuraminidase inhibitors prevent the release of influenza virus from cells, thereby limiting the infectious cycle.

When started within the first two days of flu symptoms, neuraminidase inhibitors can reduce the severity of flu symptoms and can shorten the length of the illness.^[4] There are some data to suggest that the use of these drugs can help prevent complications from the flu, such as pneumonia.^[5]

How the body affects oseltamivir phosphate

After a dose of oseltamivir phosphate is taken by mouth, over 90% is converted to the active form of the drug by the liver. This active form is eliminated from the body through the kidneys (no further liver metabolism occurs). No adjustment in the dose is needed in people who have mild to moderate liver disease. A reduction in the dose is necessary, however, in people who have severe kidney disease.

Benefits

Research has shown that using neuraminidase inhibitors, including oseltamivir phosphate, can lead to a reduction in the severity of symptoms and length of illness caused by the flu.^[4] The drugs are also about 70% to 90% effective in preventing the flu if used early enough after exposure.^[6]

Side Effects

Side effects of oseltamivir phosphate that have been reported in more than 2% of patients include the following:

• Nausea
• Vomiting
• Diarrhea
• Bronchitis (inflammation of the breathing tubes leading to the lungs)
• Stomach pain
• Dizziness
• Headache
• Cough

Risks

Roche Laboratories and the U.S. Food and Drug Administration have issued two warnings about oseltamivir. ^[7]

• The first, a letter dated December, 2003, states that the drug is not indicated or approved for the treatment or prophylaxis of influenza in children younger than one year of age.
• The second warning, posted in March of 2004, warns healthcare professionals about reports of delerium and abnormal behavior leading to injury and, in some cases, death, in Japanese patients with influenza who were taking oseltamivir. The recommendation was to carefully observe patients with influenza for any abnormal behavior and to consider discontinuing the medication if such symptoms occur.

History

Oseltamivir phosphate is marketed as in the United States as Tamiflu by Roche Laboratories.

FDA approval was granted for the treatment of influenza in October 1999. Approval for use in prevention of influenza for adolescents and adults aged 13 and older was granted in November of 2000. The drug was approved for prevention of influenza in children aged 1 to 12 in December of 2005.

Research

• In one study looking at the effectiveness of oseltamivir phosphate in the prevention of influenza, 117 healthy adult volunteers were given either oseltamivir (100 mg a day or 100 mg twice a day) or placebo (a pill with no active drug in it) and then inoculated with influenza virus in the nose. Sixty-seven percent of the placebo group developed infection with the flu virus compared with 38% of those who received oseltamivir.^[8]
• In a pivotal study assessing the effectiveness of oseltamivir phosphate for the treatment of the flu, 374 people with early influenza were randomized (assigned by chance) to receive either oseltamivir phosphate (75 mg twice a day or 150 mg twice a day) or a placebo. The length of illness was reduced by 30% in those who received oseltamivir compared with the placebo group. In addition, the severity of symptoms was reduced by 35% to 38% in participants taking oseltamivir versus those taking a placebo.^[9]
• There is increasing evidence that neuraminidase inhibitors, such as oseltamivir phosphate, may have antiviral activity against the agent of bird flu, H5N1 avian influenza virus.^{[10] [11] [12]}

Clinical Trials

A list of open clinical research trials studying the treatment of influenza can be found here

References

1. ↑ Roche Pharmaceuticals Package Insert (PDF)
2. ↑ Roberts NA. Anti-influenza drugs and neuraminidase inhibitors. Pro Drug Res. 2001;Spec No:35-77. Abstract
3. ↑ Calfee DP, Hayden FG. New approaches to influenza chemotherapy. Neuraminidase inhibitors. Drugs. 1998 Oct;56(4):537-53. Abstract
4. ↑ ^{4.0 4.1} Cooper NJ, Sutton AJ, Abrams KR, Wailoo A, Turner D, Nicholson KG. Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analyses of randomised controlled trials. BMJ. 2003 Jun 7;326(7401):1235. Abstract | Full Text | PDF
5. ↑ Gums JG, Pelletier EM, Blumentals WA. Oseltamivir and influenza-related complications, hospitalization and healthcare expenditure in healthy adults and children. Expert Opin Pharmacother. 2008 Feb;9(2):151-61. Abstract
6. ↑ Welliver R, Monto AS, Carewicz O, et al. Effectiveness of oseltamivir in preventing influenza in household contacts: a randomized controlled trial. JAMA. 2001 Feb 14;285(6):748-54. Abstract | Full Text | PDF
7. ↑ U.S. Food and Drug Administration web site. Tamiflu (oseltamivir phosphate) Information
8. ↑ Hayden FG, Treanor JJ, Fritz RS, et al. Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment. JAMA. 1999 Oct 6;282(13):1240-6. Abstract | Full Text | PDF
9. ↑ Treanor JJ, Hayden FG, Vrooman PS, et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group. JAMA. 2000 Feb 23;283(8):1016-24. Abstract | Full Text | PDF
10. ↑ American Academy of Pediatrics Committee on Infectious Diseases. Antiviral therapy and prophylaxis for influenza in children. Pediatrics. 2007 Apr;119(4):852-60. Abstract | Full Text | PDF
11. ↑ Beigel J, Bray M. Current and future antiviral therapy of severe seasonal and avian influenza. Antiviral Res. 2008 Apr;78(1):91-102. Epub 2008 Feb 4. Abstract
12. ↑ Leneva IA, Roberts N, Govorkova EA, Goloubeva OG, Webster RG. The neuraminidase inhibitor GS4104 (oseltamivir phosphate) is efficacious against A/Hong Kong/156/97 (H5N1) and A/Hong Kong/1074/99 (H9N2) influenza viruses. Antiviral Res. 2000 Nov;48(2):101-15. Abstract

External Links

U.S. Food and Drug Administration (FDA): Patient Information Sheet: Oseltamivir Phosphate

Medline Plus: Oseltamivir